MiR-200b Suppresses Gastric Cancer Cell Migration and Invasion by Inhibiting NRG1 through ERBB2/ERBB3 Signaling
Tonglei Xu, Fangliang Xie, Dazhou Xu, Weidong Xu, Xu-Ming Ge, Shengxiang Lv, Shouying Li
Abstract
PURPOSE: Accumulating evidence indicates that miRNAs (miRs) play crucial roles in the modulation of tumors development. However, the accurately mechanisms have not been entirely clarified. In this study, we aimed to explore the role of miR-200b in the development of gastric cancer (GC). METHODS: Western blot and RT-PCR were applied to detect epithelial-mesenchymal transition (EMT) marker expression and mRNA expression. Transwell assay was used for measuring the metastasis and invasiveness of GC cells. TargetScan system, luciferase reporter assay, and rescue experiments were applied for validating the direct target of miR-200b. RESULTS: MiR-200b was prominently decreased in GC tissues and cells, and its downregulation was an indicator of poor prognosis of GC patients. Reexpression of miR-200b suppressed EMT along with GC cell migration and invasion. Neuregulin 1 (NRG1) was validated as the target of miR-200b, and it rescued miR-200b inhibitory effect on GC progression. In GC tissues, the correlation of miR-200b with NRG1 was inverse. CONCLUSION: MiR-200b suppressed EMT-related migration and invasion of GC through the ERBB2/ERBB3 signaling pathway via targeting NRG1.